Acidic fibroblast growth factor (aFGF), which influences the proliferation and differentiation of various cell types in vitro, were originally isolated as single chain proteins from neural tissue, including whole brain and hypothalamus. aFGF is a heparin-dependent mitogen and it can strongly bind on all four known FGF receptors and their spliced form. It can be localized within specific subsets of neurons associated with motor and sensory functions, and can be purified from the adult brain. Purified aFGF is a mitogen for neuroblasts and promotes the neuritis extension from spinal cord neurons. In addition, aFGF was proved to promote the expression of nerve growth factors on astrocytes in culture.
It was reported in several studies that FGFs had a wide spectrum of effects on neurophysiological activities that were distinct from their mitogenic action within the central nervous system (CNS) in vivo. For instance, when administered into the brain, aFGF provided a protective effect against the degeneration of hippocampal CA1 neuron that was induced by brain ischemia (Sasaki K. et al., Brain Res. Bull. 33: 505-511, 1994). FGF1 was reported to have an effect in protecting selective neuronal populations against the neurotoxic effects of molecules involved in the pathogenesis of neurodegenerative disorders such as Alzheimer's disease (Guo, Z., and Mattson, M., Cereb. Cortex 10, 50-57, 2000) and HIV encephalitis (Everall, I. P. et al., J. Neuropathol. Exp. Neurol. 60, 293-301, 2001).
Native human aFGF polypeptide consisting of 154 amino acids was isolated from a human brain. However, the 19 amino acids from the N-terminal of the human aFGF were identified homogenous with human interleukin-1 (IL-1). The 19 amino acids from the N-terminal of the native human aFGF in common with or similar to the amino acids of IL-1 might cause the same endogenous immuno-response, including activation of macrophages, and modulate cells growth arrest (G. Venkataraman et al., P.N.A.S., 96:3658-63, 1999). Furthermore, it was reported that the pro-inflammatory cytokine IL-1 and FGF-1 (aFGF)/FGF-2 (bFGF) shared the same structural scaffold and competed against the same receptor binding site of tyrosine kinase domains (A. J. Minter et al., J. Cell Physil., 167:229-37, 1996).
Several versions of recombinant human aFGF are commercially available and widely used in various bioassays. For example, recombinant human aFGF having 140 amino acids (R&D, aa 16-155, Catalog Number: 232-FA/CF), recombinant human aFGF having 154 amino acids (R&D, aa 2-155, Catalog Number: 231-BC/CF), recombinant human aFGF having 141 amino acids (Sigma, natural sequence with an additional methionine residue attached to the N-terminus, Catalog Number: F5542). See also, Osakada F et al., Nat Protoc. 2009;4(6):811-24, and Christina Krabbe et al., J. Neurochem. (2009) 110, 1908-1920.
Furthermore, U.S. Pat. No. 7,956,033 (issued in 2011) discloses a modified human aFGF having 135 amino acids exhibiting improved stability, which comprises a native human aFGF shortened by a deletion of a deletion of 20 amino acids from N-terminal of the native human aFGF, and an addition of Alanine (Ala) before the shortened native aFGF.